Mass spectral studies reveal the structure of Aβ1-16-Cu2+ complex resembling ATCUN motif

In Alzheimer's disease, copper binds to amyloid beta (Aβ) peptide and generates oxidative stress. The coordination of histidine (His) residues to Cu(2+) is still uncertain. We studied Cu(2+) binding to Aβ1-16 peptide using the diethyl pyrocarbonate (DEPC) assay and mass spectrometry. Our results show that only one His is involved in Cu(2+) coordination, which is identified as His6 using mass spectral studies. Novel nickel displacement studies have further supported the proposal that the Cu(2+) binding site of Aβ1-16 peptide resembles the ATCUN motif of human serum albumin.